Carnitine for fatigue in multiple sclerosis
ABSTRACT Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients.
To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose.
A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011), EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied.
Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included.
Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up.
The search identified one ongoing randomized, placebo-controlled, cross-over trial (expected completion 2013) and one completed randomized, active-comparator, cross-over trial. In the completed study, adult patients with relapsing-remitting and secondary progressive MS were exposed to both acetyl L-carnitine 2 grams daily and amantadine 200 mg daily The effects of carnitine on fatigue are unclear. There was no difference between carnitine and amantadine for the number of patients withdrawing from the study due to an adverse event (relative risk ratio 0.20; 95% confidence interval 0.03 to 1.55) and no patients experienced a serious adverse event in either treatment group. Mortality and quality of life were not reported.
There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators. Results of the ongoing trial are eagerly anticipated in order to provide clarity.
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ABSTRACT: Objectives:Although fatigue is experienced by everyone, its definition and classification remains under debate. A review of the previously published data on fatigue. Fatigue is influenced by age, gender, physical condition, type of food, latency to last meal, mental status, psychological conditions, personality type, life experience, and the health status of an individual. Fatigue may not only be a symptom but also a measurable and quantifiable dimension, also known as fatigability. Additionally, it may be classified as a condition occurring at rest or under exercise or stress, as physiologic reaction or pathologic condition, as spontaneous phenomenon or triggerable state, as resistant or irresistant to preconditioning, training, or attitude, as prominent or collateral experience, and as accessible or inaccessible to any type of treatment or intervention. Fatigue may be the sole symptom of a disease or one among others. It may be also classified as acute or chronic. Quantification of fatigability is achievable by fatigue scores, force measurement, electromyography, or other means. Fatigue and fatigability need to be delineated from conditions such as sleepiness, apathy, exhaustion, exercise intolerance, lack of vigor, weakness, inertia, or tiredness. Among neurological disorders, the prevalence of fatigue is particularly increased in multiple sclerosis, amyotrophic lateral sclerosis, Parkinson disease, traumatic brain injury, stroke, and bleeding and also in neuromuscular disorders. Fatigue may be influenced by training, mental preconditioning, or drugs. Fatigue needs to be recognized as an important condition that is not only a symptom but may also be quantified and can be modified by various measures depending on the underlying cause.The American journal of hospice & palliative care 07/2013; 31(5). DOI:10.1177/1049909113494748 · 1.35 Impact Factor
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ABSTRACT: The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular and neurodegenerative. All of them are supported by the intertwined lines of evidence and none of them should be written off. However, the exact mechanisms of MS initiation, its development and progression, are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes of pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies which target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline: (i) redox processes involved in MS initiation (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potentials of antioxidative therapy.Antioxidants & Redox Signaling 03/2013; DOI:10.1089/ars.2012.5068 · 7.67 Impact Factor
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ABSTRACT: Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Current Controlled Trials ISRCTN76517470.BMC Neurology 06/2010; 10:43. DOI:10.1186/1471-2377-10-43 · 2.49 Impact Factor